Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 co-agonist tirzepatide have transformed non-surgical management of obesity and type 2 diabetes mellitus (T2DM), producing unprecedented pharmacological weight loss and cardiovascular mortality benefit. Bariatric and metabolic surgery (BMS) remains the most effective intervention for sustained weight reduction and T2DM remission. A systematic outcome-by-outcome comparison of these paradigms has not previously been synthesised. We conducted a PRISMA 2020-compliant systematic review of randomised controlled trials (RCTs) and high-quality matched observational studies (January 2014-April 2026) comparing incretin-based therapies with BMS in adults with obesity and T2DM. Primary outcomes were T2DM remission, weight reduction, major adverse cardiovascular events (MACE) and all-cause mortality, non-alcoholic steatohepatitis (NASH) resolution, and quality of life (QoL). Secondary outcomes included HbA1c, lipids, blood pressure, renal endpoints, and safety. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) and Newcastle-Ottawa Scale; certainty was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Fourteen studies met inclusion criteria (eight RCTs, six matched cohorts; N=25,566). BMS achieved superior T2DM remission (23-70% vs. 0%), greater sustained five-year weight loss (25-32% vs. 14.9-20.9% with semaglutide/tirzepatide, with significant pharmacological weight regain upon discontinuation), and lower MACE risk (pooled RR 0.48, 95% CI 0.33-0.72 vs. GLP-1 RAs; P<0.001). BMS was also superior for NASH histological resolution (56-70% vs. 59% with semaglutide) and QoL. Incretin therapies produced clinically meaningful cardiometabolic improvements with favourable safety profiles dominated by transient gastrointestinal events. Tirzepatide 15 mg approached but did not match sleeve gastrectomy weight-loss benchmarks at 72 weeks. BMS demonstrates superiority across all five primary outcome domains in patients with obesity and established T2DM. Incretin therapies remain essential for those who decline, defer, or are contraindicated for surgery. Complementary and sequential use - incretins as a bridge to or adjunct following surgery - warrants prospective evaluation. Guidelines should position BMS as a first-line option in appropriate candidates.
